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Hagan H.,University of South Africa | Hagan H.,New York University | Pouget E.R.,National Development and Research Institutes | Williams I.T.,Centers for Disease Control and Prevention | And 6 more authors.
Journal of Infectious Diseases | Year: 2010

Background. In studies of hepatitis C virus (HCV) seroconversion in injection drug users (IDUs), some have questioned whether underreporting of syringe sharing, a stigmatized behavior, has led to misattribution of HCV risk to other injection-related behaviors. Methods. IDUs aged 15-30 years who were seronegative for human immunodeficiency virus and HCV antibodies were recruited into a prospective study in 5 US cities. Behavioral data were collected via computer-assisted self-interviewing to reduce socially desirable reporting. Hazard ratios (HRs) were estimated to assess associations between behavior and HCV seroconversion. Because the shared use of cookers, cottons, and rinse water was highly correlated, a summary variable was created to represent drug preparation equipment sharing. Results. Among 483 IDUs who injected during the period covered by the follow-up assessments, the incidence of HCV infection was 17.2 cases per 100 person years; no HIV seroconversions occurred. Adjusting for confounders, the shared use of drug preparation equipment was significantly associated with HCV seroconversion (adjusted HR, 2.66; 95% confidence interval, 1.03-23.92), but syringe sharing was not (adjusted HR, 0.91). We estimated that 37% of HCV seroconversions in IDUs were due to the sharing of drug preparation equipment. Conclusions. Associations between sharing drug preparation equipment and HCV seroconversion are not attributable to underascertainment of syringe sharing. Avoiding HCV infection will require substantial reductions in exposure to all sources of contaminated blood. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Ehrlich R.I.,University of Cape Town | Myers J.E.,University of Cape Town | Te Water Naude J.M.,Asbestos Relief Trust | Thompson M.L.,University of Cape Town | And 2 more authors.
Occupational and Environmental Medicine | Year: 2011

Objective: To estimate exposure-response relationships between respirable dust, respirable quartz and lung function loss in black South African gold miners. Methods: 520 mineworkers aged >37 years were enrolled in a cross-sectional study. Gravimetric dust measurements were used to calculate cumulative respirable dust and quartz exposures. Excess lung function loss was defined as predicted minus observed forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The association between excess loss and exposure was estimated, adjusting for smoking, tuberculosis and silicosis. Results: Mean service length was 21.8 years, mean respirable dust 0.37 mg/m3 and mean respirable quartz 0.053 mg/m3. After adjustment, 1 mg-yr/m3 increase in cumulative respirable dust exposure was associated with 18.7 ml mean excess loss in FVC [95% confidence interval (CI) 0.3, 37.1] and 16.2 ml in FEV1 (95% CI -0.3, 32.6). Mean excess loss with silicosis was 224.1 ml in FEV1 and 123.6 ml in FVC; with tuberculosis 347.4 ml in FEV1 and 264.3 ml in FVC. Conclusion: Despite a healthy worker effect, lung function loss was demonstrable whether due to silicosis, tuberculosis or an independent effect of dust. A miner working at a respirable dust intensity of 0.37 mg/m3 for 30 years would lose on average an additional 208 ml in FVC (95% CI 3, 412) in the absence of other disease, an impact greater than that of silicosis and comparable to that of tuberculosis. Improved dust control on the South African gold mines would reduce the risk of silicosis, tuberculosis and lung function impairment.

Ferguson L.,London School of Hygiene and Tropical Medicine | Ferguson L.,University of Nairobi | Lewis J.,London School of Hygiene and Tropical Medicine | Lewis J.,Aurum Institute for Health Research | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2012

Background: There has been little attention, until recently, to linking women who test HIV positive in pregnancy-related services to long-term HIV care and treatment services. Methods: A retrospective review of routine hospital data was carried out in 2 hospitals in Kenya. Associations between available demographic information and uptake of HIV-related services within 6 months of HIV diagnosis in pregnancy-related services were assessed using logistic regression. Kaplan-Meier survival analysis was used to assess time between HIV diagnosis and registration at the HIV clinic. Referrals between pregnancy-related and HIV-related services were observed. Results: At Naivasha hospital, the proportion of women registering at the HIV clinic within 6 months was 17.2% (153 of 892); at Gilgil hospital, it was 35.4% (84 of 237). Highly active antiretroviral therapy (HAART) was initiated by 40% and 27% of known eligible women in Naivasha and Gilgil, respectively. Non-systematic registration of clients on first contact at the HIV clinic, and restricted availability of services due to costs and opening hours were observed. In Naivasha, year, attendance at multiple pregnancy-related visits, and attendance at antenatal care in Naivasha hospital were associated with registration at the HIV clinic. In Gilgil, year, attendance at multiple pregnancy-related visits, and women being in their first pregnancy were associated with the outcome. Conclusions: Only 4% of women estimated to need HAART for their own care initiated HAART within 6 months of HIV diagnosis. Challenges associated with providing longitudinal care are especially evident in the context of high population mobility. Innovation in service delivery is required to improve uptake of services. © 2012 Lippincott Williams & Wilkins.

Gray G.E.,University of Witwatersrand | Gray G.E.,South African Medical Research Council | Moodie Z.,Fred Hutchinson Cancer Research Center | Metch B.,Fred Hutchinson Cancer Research Center | And 15 more authors.
The Lancet Infectious Diseases | Year: 2014

Background: The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. Methods: HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18-35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Findings: Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31-42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13-2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2-9·5] for vaccine recipients vs 8·8% [7·1-10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. Interpretation: The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines. Funding: National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council. © 2014 Elsevier Ltd.

Lawn S.D.,Institute for Infectious Disease and Molecular Medicine | Lawn S.D.,London School of Hygiene and Tropical Medicine | Wood R.,Institute for Infectious Disease and Molecular Medicine | De Cock K.M.,HIV | And 7 more authors.
The Lancet Infectious Diseases | Year: 2010

Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy. © 2010 Elsevier Ltd. All rights reserved.

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